Neurodegeneration affects millions of Americans each year, occurring in later periods of life, where its onset is induced by neuroinflammation and oxidative stress. Flavonoids are known to protect against damages caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS). This study evaluated the effect of hesperetin (HST), a major flavonoid found in oranges and mandarins, on LPS-activated BV-2 microglial cells. The obtained results of RT-PCR showed that HST down-regulated the mRNA expression of PD-L1 in more than 50% of the LPS-activated cells. In addition, HST induced the mRNA expression of Nrf2, which is involved in the transcription of several antioxidant genes. Moreover, the data from the oxidative stress PCR arrays showed that after 24 h, the concentration of 100 µM of HPT modulated numerous genes that regulate oxidative stress and inflammatory processes. HST down-regulated the mRNA expression of ERCC6, ACTB, SQSTM11, NOS2, and NCF1 and up-regulated the expression of HMOX1, which participate not only in excessive oxidative stress processes, by also in exacerbated inflammatory states. Both CAT and SOD enzymatic assays showed that treatment with HSP and LPS alone had no effect on CAT expression, but when cells were treated with the combination of HST and LPS, there was a reduction in these expressions enzymes. The quantitative glutathione assays demonstrated that only the combination treatment of HST and LPS reduced the expression of glutathione after a 24-h treatment period. In conclusion, these data show that hesperetin modulates several genes associated with oxidative stress and neuroinflammation and may potentially slow the progression of neurodegeneration.
